NCT07148791

Exploratory Study of Anti-BCMA-CD19 CAR-T Cell Therapy in Relapsed or Refractory IgG4-Related Disease

Exploratory Clinical Study of Anti-BCMA-CD19 CAR-T Cell Therapy for Relapsed/Refractory IgG4-Related Disease

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 9 (estimated)
• Sponsor: Chinese PLA General Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to test the safety and potential benefit of a new immune cell therapy called anti-BCMA-CD19 CAR-T cells in adults (18-75 years) with IgG4-related disease (IgG4-RD) that has come back or not improved after standard treatments such as glucocorticoids or rituximab. The main questions this study aims to answer are: * What medical problems (side effects) occur after receiving anti-BCMA-CD19 CAR-T cell therapy? * Does anti-BCMA-CD19 CAR-T cell therapy improve IgG4-RD disease activity scores at 12 weeks and 26 weeks? Participants will: * Have their own blood immune cells collected by a procedure called leukapheresis * Receive short-term chemotherapy to prepare the immune system * Receive one intravenous infusion of anti-BCMA-CD19 CAR-T cells * Return for regular clinic visits over 26 weeks for safety checks, blood tests, and imaging * May be followed for up to one year in total

Detailed description

This is a Phase 2, open-label, single-arm exploratory clinical trial using a 3+3 dose-escalation design to assess the safety, feasibility, and preliminary efficacy of autologous anti-BCMA-CD19 chimeric antigen receptor T (CAR-T) cell therapy in patients with relapsed or refractory IgG4-related disease (IgG4-RD). Background IgG4-RD is a chronic, immune-mediated fibroinflammatory disorder that can involve multiple organs, including the pancreas, bile ducts, salivary glands, kidneys, lungs, and retroperitoneum. Although standard treatments such as glucocorticoids and anti-CD20 monoclonal antibodies (e.g., rituximab) are effective for most patients, some develop treatment resistance, frequent relapses, or contraindications to conventional immunosuppressive agents. This creates an unmet clinical need for novel therapeutic strategies. Recent translational studies show that IgG4-RD lesions often contain abundant CD19+ B cells, plasmablasts, and long-lived plasma cells expressing B-cell maturation antigen (BCMA), many of which may be resistant to conventional B-cell depletion. Dual-target CAR-T cells directed against both CD19 and BCMA may achieve more complete depletion of pathogenic B-lineage cells and offer a promising treatment for refractory IgG4-RD. Methods Eligible participants will undergo leukapheresis for autologous peripheral blood mononuclear cell (PBMC) collection. Cells will be transduced ex vivo with a lentiviral vector encoding a CAR construct targeting CD19 and BCMA, then expanded and prepared for infusion. Lymphodepletion chemotherapy with cyclophosphamide (250 mg/m\^2/day, IV) and fludarabine (30 mg/m\^2/day, IV) will be given on Days -5 to -3. The doses of fludarabine and cyclophosphamide may be adjusted based on the patient's condition. CAR-T cells will be infused on Day 0 at one of three sequential dose levels (1×10\^6, 2×10\^6, or 3×10\^6 CAR+ T cells/kg, ±20%). Participants will be followed regularly for safety (adverse events \[AEs\], serious adverse events \[SAEs\], cytokine release syndrome \[CRS\], immune effector cell-associated neurotoxicity syndrome \[ICANS\]), pharmacokinetics (CAR-T cell expansion and persistence), and immunologic responses. Endpoints The primary endpoints are safety (incidence of dose-limiting toxicities \[DLTs\] within 28 days post-infusion) and efficacy (change in IgG4-RD Responder Index \[RI\] at Week 12 and Week 26). Secondary endpoints include changes in target lesion size, serum IgG4, IgE, and eosinophil counts, as well as histopathologic changes in affected tissue. Exploratory Analyses Exploratory studies will assess immune cell profiles in blood, bone marrow, and tissue biopsies using flow cytometry, multiplex cytokine assays, and spatial or single-cell transcriptomic techniques.

Conditions

• IgG4 Related Disease
• B-cell Mediated Autoimmune Disorders

Interventions

Type	Name	Description
BIOLOGICAL	Anti-BCMA-CD19 CAR-T cells	Anti-BCMA-CD19 CAR-T cell injection is an autologous, dual-target chimeric antigen receptor T-cell therapy designed to target CD19 and BCMA antigens. Peripheral blood mononuclear cells (PBMCs) are collected from each participant and modified ex vivo using lentiviral transduction to express the CAR construct. Lymphodepletion with cyclophosphamide (250 mg/m\^2/day, IV) and fludarabine (30 mg/m\^2/day, IV) is administered for 3 days (Day -5 to Day -3). The doses of fludarabine and cyclophosphamide may be adjusted based on the patient's clinical condition. CAR-T cells are infused intravenously on Day 0 at one of three dose levels (1x10\^6, 2x10\^6, or 3x10\^6 CAR+ T cells/kg, ±20%). This product is being investigated in patients with relapsed or refractory IgG4-related disease (IgG4-RD) to assess safety and preliminary efficacy.

Timeline

• Start date: 2025-09-05
• Primary completion: 2027-09-01
• Completion: 2029-12-31
• First posted: 2025-08-29
• Last updated: 2025-09-03

Locations

1 site across 1 country: China